Long noncoding RNA MALAT1 knockdown inhibits progression of anaplastic thyroid carcinoma by regulating miR-200a-3p/FOXA1

Cancer Biol Ther. 2019;20(11):1355-1365. doi: 10.1080/15384047.2019.1617567. Epub 2019 Sep 10.


Long noncoding RNAs (lncRNAs) have been reported to play essential roles in progression of thyroid carcinoma. However, the roles of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in anaplastic thyroid carcinoma (ATC) process and its mechanism remain not been fully established. In this study, we focused on the effect of MALAT1 on cell proliferation, apoptosis, migration, invasion, and autophagy formation in ATC and explored the interaction between miR-200a-3p and MALAT1 or FOXA1. Moreover, murine xenograft model was established to investigate the roles and mechanism of MALAT1 in ATC progression in vivo. Results showed that MALAT1 expression was enhanced and miR-200a-3p was reduced in ATC tissues and cells. Knockdown of MALAT1 or overexpression of miR-200a-3p inhibited cell proliferation, migration and invasion but increased apoptosis and autophagy formation in ATC cells. Moreover, miR-200a-3p was directly bound to MALAT1 and its inhibition reversed the inhibitory effect of MALAT1 knockdown on progression of ATC. In addition, FOXA1 was indicated as a target of miR-200a-3p and its restoration attenuated the anti-cancer role of miR-200a-3p in ATC cells. Furthermore, MALAT1 functioned as a competing endogenous RNA (ceRNA) via sponging miR-200a-3p to derepress FOXA1 expression. Besides, interference of MALAT1 decreased tumor growth by upregulating miR-200a-3p and downregulating FOXA1. Collectively, MALAT1 knockdown suppressed ATC progression by regulating miR-200a-3p/FOXA1, providing a novel avenue for treatment of ATC.

Keywords: Anaplastic thyroid carcinoma; FOXA1; MALAT1; miR-200a-3p.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / genetics
  • Hepatocyte Nuclear Factor 3-alpha / genetics*
  • Heterografts
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • RNA, Long Noncoding / genetics*
  • Thyroid Carcinoma, Anaplastic / genetics*
  • Thyroid Carcinoma, Anaplastic / pathology


  • FOXA1 protein, human
  • Hepatocyte Nuclear Factor 3-alpha
  • MALAT1 long non-coding RNA, human
  • MIRN200 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding